The Prevalence of Indian Common Krait Envenomation

Ramaswamy et al Journal of Drug Delivery & Therapeutics. 2018; 8(2):158-162

Available online on 15.03.2018 at http://jddtonline.info Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

Open Access Review Article THE PREVALENCE OF INDIAN COMMON KRAIT ENVENOMATION AND ITS CLINICAL COMPLICATIONS AMONG THE RURAL POPULATIONS OF INDIA Malathi Ramaswamy*, Sivakumar Duraikannu, Chandrasekar Solaimuthu Research Department of Biotechnology, Bharathidasan University Constituent College, Perambalur district, Tamil Nadu state, India, Pin code – 621 107

ABSTRACT Snake envenomations have been a serious yet often overlooked public health threat especially in tropical and subtropical countries, including Southeast Asia. The medically important venomous land snakes in Southeast Asia include snakes from the Elapidae and Crotalidae families. Among the elapids, there are only 12 species that are considered of medical importance, represented by the kraits (Bungarus caeruleus, B. candidus, B. fasciatus, B. flaviceps and B. multicinctus). The incidence of snakebite is high in India. Apart from mortality, the morbidity is due to various complications. The common krait (Bungarus caeruleus) is the most toxic snake found commonly in the plains of throughout the India and the number of snakebites in the rural areas of India was recorded by this snake. The present article highlights the prevalence and the clinical complications of Indian common krait envenomation among the rural populations of India. Keywords: snake bite, common krait, clinical complications and rural area

Article Info: Received 16 Jan, 2018; Review Completed 3 March, 2018; Accepted 4 March, 2018; Available online 15 March, 2018 Cite this article as:

Ramaswamy M, Duraikannu S, Solaimuthu C, The prevalence of Indian common krait envenomation and its clinical complications among the rural populations of India, Journal of Drug Delivery and Therapeutics. 2018; 8(2):158-162 DOI: http://dx.doi.org/10.22270/jddt.v8i2.1676

*Address for Correspondence Dr. R. Malathi, Assistant Professor and Head, Department of Biotechnology, Bharathidasan University Constituent College, Kurumabalur, Perambalur – 621107, Tamilnadu, India

INTRODUCTION (Kasturiratne et al., 2008; Chippaux, 2006). The medically important venomous land snakes in Southeast Alexander the Great who invaded India in 326 BC, was Asia include snakes from the Elapidae and Crotalidae greatly impressed by the skills of Indian physicians, families. Among the elapids, there are only 12 species especially in the treatment of snakebites (Jaggi, 2000). that are considered of medical importance, represented Since then, India has remained notorious for its by the kraits (Bungarus caeruleus, B. candidus, B. venomous snakes and the effects of their bites. With its fasciatus, B. flaviceps and B. multicinctus), the Asiatic surrounding seas, India is inhabited by more than 60 cobras (including Naja kaouthia, N. sumatrana, N. species of venomous snakes, some of which are siamensis, N. sputatrix, N. philippinensis and N. atra), abundant and can cause severe envenoming (Whitaker, and the king cobra (Ophiophagus hannah) (Warrell, 2004). 1999). Snake envenomations have been a serious yet often The incidence of snakebite is high in India. Apart from overlooked public health threat especially in tropical and mortality, the morbidity is due to various complications subtropical countries, including Southeast Asia ISSN: 2250-1177 [158] CODEN (USA): JDDTAO Ramaswamy et al Journal of Drug Delivery & Therapeutics. 2018; 8(2):158-162 (Narvencar, 2006). Approximately 10000 to 50000 species are hunting for rodents. Bites generally occur snakebite related deaths occur in India each year when kraits are disturbed by sleeping humans moving, (McNamee, 2001). A majority of the deaths are caused either naturally, or during rapid eye movement (REM) by neurotoxic envenoming by kraits and cobras in sleep (Kularatne, 2002). India’s rural population (McNamee, 2001; Warrell, The major neurotoxic component of krait venom is β- 1999). Snakebite is common in subtropical countries bungarotoxin, which has high affinity for presynaptic with heavy rainfall and humid climates (Banerjee, 1978). neuromuscular receptors. It irreversibly blocks these Snake bite affects South Asia than anywhere else in the receptors and is completely resistant to world with very high morbidity and mortality. anticholinesterase treatment (Watt et al., 1986). Identification of the offending snake often facilitates Components of krait venom clinical management of the patient (Alirol, et al., 2010). Awareness of the fact had led the public to carry Krait venom possess a wide variety of toxins and offending snakes killed or alive, to hospital together with enzymes including neurotoxins, membrane toxins, snake bite victims when possible. However, even if the cardiotoxins, 3 finger toxins (3FTXs), PLA2s, offending snake is authenticated, incorrect metalloproteinases, cholinesterases, L-amino acid authentications also had led to inappropriate oxidases, serine proteases etc. (Rusmili et al, 2014). α- management (Nishioka and Silveira, 1994; Ariaratnam bungarotoxin, the first postsynaptic neurotoxin isolated et al., 2009). from Bungarus multicinctus, inhibited the response of acetylcholine receptor on motor endplate and Some snake species are often misidentified due to irreversibly blocked the transmission (Chang and Lee, morphological resemblance to other snakes. For 1963; Lee and Chang, 1966; Jiang et al, 1986). The example, highly venomous Kraits are often misidentified other postsynaptic neurotoxins isolated from Bugnagus as non-venomous Wolf snakes or vise-versa due to sp. include TI, TH, κ-bungarotoxin, κ 2-bungarotoxin notoriously similar colour patterns (Fernando, 1997). and κ 3-bungarotoxin, ceruleotoxin, alphaN3 and Bucain Immunodiagnostic techniques like Enzyme linked (Hsu et al, 1985; Grant and Chiappinelli, 1985; Immunosorbent Assay is increasingly being used to Chiappinelli et al, 1990; Bon et al, 1975; Karsani and accurately authenticate the offending snake in snake bite Othman, 2009; Murakami et al, 2009). β-bungarotoxin, cases in some countries (Ho et al., 1986). However, γ-bungarotoxin and Toxin F are presynaptic neurotoxins since these techniques are not yet available in routine isolated from Bugnagus sp. Venom (Chang and Lee, practice in India, conventional snake identification 1963; Rehm and Betz, 1984; Tsai et al, 2007; Chang et methods like morphological studies are still useful. al, 2002; Loring et al, 1984). Phospholipase A2 (PLA2) is also an important constituent of Bungarus sp. venom Indian common krait (Bungarus caereulus) (Liu et al., 1988; Liu et al., 1989; Khow et al., 2002; The B. caeruleus snake has strong neurotoxic venom, Tsai et al, 2007). The enzyme L-amino acid oxidase envenomation by B. caeruleus causes hemorrhage, tissue (LAAO) found in Bungagus sp. venom plays a major necrosis and hemostatic disorders in the experimental role in inducing toxicity (More et al, 2010; Wei et al, animal. Furthermore, it shows high proteolytic activity 2009). A number of protease inhibitors have been towards casein and human fibrinogen (Rajana et al., identified from krait venom (Zhang et al, 1995; Lu et al., 2013). 2008; Chen et al., 2015; Siang et al., 2010; Khow et al., 2003). Cholinesterase was also purified from B. The common krait (Bungarus caereulus) is regarded as fasciatus venom through fractional precipitation with the most dangerous species of venomous snake in the ammonium sulfate (Ghosh and Chaudhuri, 1968). Indian subcontinent (Theakston et al., 1990). The most villagers in India usually sleep on the floor of their area, Clinical complications of Krait venom: which are often surrounded by dense vegetation Envenoming due to krait (Genus: Bungarus) bites is a (Bawaskar, 2002). Although not vicious by nature, the common, serious health issue in South and South-East krait may strike a person sleeping on the ground if the Asia. Common krait (Bungarus caeruleus) is distributed person accidentally touches or rolls over onto the snake throughout South Asia, and is responsible for large (Kulartane, 1997). Also, the snake could mistakenly numbers of cases of severe neurotoxic envenoming each identify an exposed body part as prey. Most bites occur year (Valenta, 2010). It results in a descending flaccid during the cooler months of June to December when paralysis progressing to life threatening respiratory snakes may, during the course of their hunting activity, paralysis unless mechanical ventilation is available linger in a person’s bedding to take advantage of the (Alirol et al., 2010; Pe et al., 1997; Kularatne, 2002). warmth therein (Bawaskar, 2002; Kulartane, 1997). The Krait bites typically occur at night and are not painful; common krait (Bungarus caeruleus) is the most toxic so many patients do not notice the bite and continue snake found commonly in the plains of Northwest India sleeping (Bawaskar and Bawaskar, 2004; Warrell et al., and bites typically occur during July—September 1983; Ariaratnam et al., 2008), which delays medical (Sharma et al., 2005; Chauhan et al., 2005; Aggarwal et care. Neuromuscular paralysis in krait envenoming is al., 2005). Kraits are elapid snakes and within the single characterized by progressive descending paralysis. Krait genus Bungarus, 12 species are found (Keogh, 1998). venom contains β-bungarotoxins, which are presynaptic They are generally nocturnal, shy and non-aggressive. neurotoxins with phospholipase A activity and Their diet consists of other snakes and it will therefore considered to be the major cause of paralysis. The pre- pursue them into human habitation, where the prey synaptic action is irreversible and is the reason that once

ISSN: 2250-1177 [159] CODEN (USA): JDDTAO Ramaswamy et al Journal of Drug Delivery & Therapeutics. 2018; 8(2):158-162 paralysis develops it is not reversed with antivenom 1895, against the Indian cobra (Naja naja). Antivenom (Dixon, 1999). binds to and neutralizes the venom, stopping further damage, but do not reverses the damage already done. The pathophysiology of neuromuscular paralysis in Some individuals may react to the antivenom with snake envenoming remains poorly understood. This is immediate hypersensitivity reactions. Other alternative due to the lack of detailed clinical studies of treatment involves the usage of folk and traditional authenticated bites that report the time course of medicines in snake bites. Medicinal herbs are the local paralysis, including the recovery of paralysis, and very heritage in the global importance. Various plants have few studies of neurophysiological function in snake been used against snake bite, in folk and traditional envenoming. There is also little evidence for the medicine. In Ayurvedic system of medicine different effectiveness of antivenom in reversing neuromuscular plants and their compounds are reported to possess paralysis (Johnston, et al., 2012). Neurophysiological antisnake venom activity. But they also possess these testing could provide objective evidence of the individual toxicities and most of the folk medicinal progression and recovery of neurotoxicity, and the plants have no scientific validation (Gomes et al., 2010; response to antivenom. Previous neurophysiological Cannon et al., 2008). testing in krait bites with nerve conduction studies and repetitive nerve stimulation tests provide some Currently, a large number of plants and plant materials information on krait neurotoxicity. Single fibre electro- are being screened for pharmacological activities myography (sfEMG) is a more sensitive test of especially those used in traditional or folk medicine neuromuscular function (Richardson, et al., 2007). It has against different diseases. Over the years, many attempts only been reported in one study of neuromuscular have been made for the development of snake venom paralysis from Papuan taipan envenoming (Sanders, antagonists especially from plant sources in spite of the 2002). Better methods to measure neuromuscular existence of antiserum. Many Indian medicinal plants or dysfunction in neurotoxic envenoming will improve our plant materials are recommended for the treatment of understanding of neuromuscular paralysis and the snakebite and some are tested, but so far no systematic clinical benefit of antivenom. analysis has been done (Alam and Gomes, 2003; Chopra, et al., 1956; Nazimudeen et al., 1978). Clinical complications: The common krait (Bungarus caeruleus) is the most Indian Krait is distributed in India, Bangladesh, toxic snake found commonly in the plains of Northwest Pakistan, Nepal and Sri Lanka. Bites by these snakes India and bites typically occur during July—September lead to high morbidity and mortality in the region, often (Sharma et al., 2005; Chauhan et al., 2005; Aggarwal et leading to death of the victim, if not intervened (Warrell, al., 2005). Kraits are elapid snakes and within the single 1995). Indian Krait is known to cause most of the bites genus Bungarus, 12 species are found (Keogh, 1998). during night, when the victim is sleeping (Kularatne, They are generally nocturnal, shy and non-aggressive. 2002). Indian Kraits cause a clinical syndrome Their diet consists of other snakes and it will therefore characterized by negligible local envenoming, vomiting, pursue them into human habitation, where the prey abdominal pain and descending paralysis that at times species are hunting for rodents. Bites generally occur start as soon as 30 min after the bite which could be when kraits are disturbed by sleeping humans moving, delayed for up to 4 h (Ariaratnam et al., 2008). Although either naturally, or during rapid eye movement (REM) ptosis, external opthalmoplegia, dysphagia, drowsiness, sleep (Kularatne, 2002). A significant number of patients altered consciousness and deep coma also had been die before they reach the hospital, largely due to the fact commonly reported following envenoming by this that the bite does not inflict sufficient pain or as a result snake, reports on prolonged WBCT in Indian Krait bite of the bite itself or venom action and the victims are victims has been very rare (Kularatne, 2002). On the therefore unaware that they have been bitten. contrary, Sri Lankan Russell’s viper (Daboia russelli) frequently causes both neurotoxicity and coagulopathy Common venomous snakes found in the Indian in the victims (Kularatne, 2003). However, Kularatne subcontinent are kraits, cobras, and carpet vipers (Echis reported mottling haemorrhages in viscera and adrenal carinatus). Kraits are nocturnal, terrestrial snakes that bleeding in one victim of Indian Krait who died due to enter human dwellings in search of prey such as rats, shock, however with no clinical details (Kularatne, mice, and lizards (Bawaskar, 2002). 2002). In addition, the same study revealed occurrence Spectacled cobra (Naja naja), common krait (Bungarus of mucosal haemorrhages in stomach of 3 of the 16 caeruleus), saw-scaled viper (Echis carinatus) and deceased victims of Indian Krait bite. Therefore, altered Russell's viper (Daboia russelii) have long been coagulation and haemorrhages as evident from the recognised as the most important, but other species may laboratory and post-mortem findings of the victim cause fatal snakebites in particular areas, such as the suggest rare clinical presentations of anti-coagulant central Asian cobra (Naja oxiana) in the far north-west, effects of Indian Krait venom. monocellate cobra (N. kaouthia) in the north-east, Treatment of Snakebite: greater black krait (B.niger) in the far north-east, Wall's and Sind kraits (B. walli and B. sindanus) in the east and The treatment of snakebite is as variable as the bite west and hump-nosed pit-viper (Hypnale hypnale) in the itself. The only available treatment is the usage of south-west coast and Western Ghats (Whitaker, 2004). antivenom against snakebite. The first antivenom (called an anti-ophidic serum) was developed by Albert Calmette, a French scientist of the Pasteur Institute in

ISSN: 2250-1177 [160] CODEN (USA): JDDTAO Ramaswamy et al Journal of Drug Delivery & Therapeutics. 2018; 8(2):158-162 Herbal remedies for Snakebite practitioners of witchcraft, especially in developing countries. It has been reported that in most developing Extracts from plants have been used among traditional countries, up to 80% of individuals bitten by snakes first healers, especially in tropical areas where there are consult traditional practitioners before visiting a medical plentiful sources, as therapy for snakebite for a long centre. Owing to the delay, several victims die during time. Several medicinal plants, which appear in old drug journey to the hospital (Hasson et al., 2009) recipes or which have been passed on by oral tradition, are believed to be snakebite antidotes. Many Indian CONCLUSION medicinal plants are recommended for the treatment of Snakebite is being one of the dangerous health hazards snakebite (Meenatchisundaram et al., 2008). Accurate in tropical countries especially in India. The data present records to determine the exact epidemiology or even in this paper will help the reader to understand the snake mortality of snake bite cases are generally unavailable. venom, Indian common krait, composition of krait Hospital records fall far short of the actual number, venom and the clinical complications of the krait bite owing to dependence on traditional healers and treatment.

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